PI3K/Akt/mTOR · target hub

HRAS

GTPase HRas (HRAS)

HRAS is a Upstream RTK–Ras–MAPK node on the PI3K/Akt/mTOR axis. Involved in the activation of Ras protein signal transduction (PubMed:22821884). Ras proteins bind GDP/GTP and possess intrinsic GTPase activity (PubMed:12740440, PubMed:14500341, PubMed:9020151) It is indexed under "Ras / MAPK & adaptors (RTK→PI3K bypass)" on our pathway page for antibodies, inhibitors, and assay guidance.

Back to pathway overviewSearch: HRASUniProt (P01112)

Research notes

  • Combine with other genes in the same hub block via genetics or pharmacology to test non-redundant roles of HRAS.
  • Annotate PIK3CA/PTEN and upstream RTK–Ras context when reading p-AKT, mTORC1/2, or lipid outputs.
  • Verify antibody clone, phospho-site, and stimulation; include KD/KO or inhibitor controls.

On the pathway hub (sections)

Activating lesions & amplification (quick reference)

Type / exampleDomain / context (brief)
Kinase domainKinase-domain activating lesions (RTK-dependent)
Fusion / amplificationFusion or amplification (cohort-dependent)
CN gainCopy gain and overexpression

Naming and prevalence vary by cohort and assay—annotate clinically with COSMIC, ClinVar, OncoKB, and datasheets; research context only.

Assay readouts for HRAS

  • Receptor phosphorylation: p-RTK or p-Tyr blots—ligand time courses.
  • Downstream: p-AKT and p-ERK—partition PI3K vs MAPK dependence.
  • Genetics: KRAS/BRAF/PTEN context; bypass on resistance.
  • Inhibitor matrix: RTK/MEK/PI3K-selective agents.

HRAS experimental notes

Examples below reflect common literature and public resources (e.g., CCLE, DepMap)—validate genotypes, expression, and passage in your own stocks before committing assays.

[1] Cell lines commonly used for HRAS studies (examples)

  • Tool lines: A549, HepG2, PC-9, Ba/F3, HEK293T—screen by HRAS expression and pathway context (CCLE/DepMap).
  • Combine with neighbors (KRAS, NRAS, MRAS, RRAS) via KD/pharmacology to test non-redundancy.
  • Overexpression/rescue in HEK293T supports mechanism and IP workflows.
  • Isogenic/CRISPR models separate pathway dependency from bypass survival.

[2] Cell samples for HRAS Western blot

  • Whole-cell lysates—optimize RIPA/NP-40 per antibody; phosphatase inhibitors for phospho blots.
  • Stimulation: serum starvation ± insulin/EGF or amino-acid withdrawal/refeed as relevant.
  • Controls: siRNA/shRNA, CRISPR KO, or inhibitors to validate band specificity.
  • Loading: BCA normalization; subcellular fractionation when needed.

[3] Tissue samples for HRAS Western blot

  • Matched tumor/adjacent frozen tissues after pathology review.
  • Mouse GEMM or xenografts—mind species antibody cross-reactivity.
  • Primary cells/PDCs when ethically approved.
  • FFPE needs specialized extraction; frozen tissue preferred for phospho work.

[4] Cell samples for HRAS immunoprecipitation

  • Tagged overexpression: HEK293T FLAG/HA-HRAS for complex capture.
  • Endogenous IP: high-expression lines; often ≥1–5×10⁶ cells per IP.
  • Stimulation: ligand or nutrient treatments enrich interactions—pilot time courses.
  • Controls: isotype IgG, empty vector, KD/KO negatives.

Human tissues and primary cells require ethics/IRB approval; tumors are heterogeneous—record histotype, site, and preservation conditions.

Bypass & related pathways

Models & genetics note

Overexpression vs endogenous HRAS can differ in dosage, splicing, and compartmentation—in organoids/PDX, record passage, matrix, and drug history.

Quick search presets

HRASHRAS antibodyPI3K inhibitormTOR inhibitor

HRAS-related antibodies (keyword-biased)

Adds HRAS keyword bias atop the PI3K/Akt/mTOR antibody pool—if sparse, use presets above or global search.

Neighboring targets (same hub)

KRASNRASMRASRRASRRAS2GRB2GAB1GAB2

External databases & resources

FAQ

This content supports research reagents and pathway education—not medical advice. Annotate mutations, drug indications, and protocols with authoritative databases, datasheets, and institutional oversight.

Last reviewed: 2026-05-18

Related on this site

See the PI3K/Akt/mTOR hub for neighboring nodes and assay guidance—cross-check MAPK, RTK, metabolism, and autophagy pages as needed.

PI3K/Akt/mTOR·MAPK/ERK·Receptor tyrosine kinase·Metabolism